Chapter 13: Signal Transduction Pathways Flashcards

1
Q

Signal transduction is critical because…

A

Allows organism to sense its environment and formulate a biochemical response

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2
Q

5 Steps of the Signal transduction pathway

A
  1. Release of a primary message
  2. Reception
  3. Relay - secondary messengers
  4. Activation
  5. Termination
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3
Q

A low [] of signal in the environment (outside) can yield a…..

A

Large intracellular signal and response (inside)

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4
Q

What are the 3 major classes of membrane receptors?

A
  1. Seven-transmembrane helix (7TM) receptors associated with heterotrimeric G-proteins
  2. Dimeric membrane receptors that recruit protein kinases
  3. Dimeric protein receptors that are protein kinases (both receptor and kinase functions)
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5
Q

The most common receptors in signaling events are?

A

7TM receptors have a host of functions!

They mediate hormone action, secretion, neurotransmission, chemotaxis, exocytosis, control of blood pressure, embyrogenesis, cell growth, development, smell, taste, vision, viral infection

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6
Q

Several thousand 7TM receptors exist. What % of currently used drugs target these receptors?

A

50%

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7
Q

7TM receptors have _________ and ___________.

A

Seven alpha-helices and span the membrane bilayer

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8
Q

Ligand epinephrine receptor binds to B-adrenergic receptor. What happens? Why?

A

Change in conformation to allow the signal to be able to be detected inside the cell

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9
Q

The unactivated G-protein is a heterotrimer consisting of…

A

An alpha subunit, bound to GDP and beta and gamma subunits.

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10
Q

After binding epinephrine, the beta-adrenergic receptor activates a…

A

Heterotrimeric G-preitein

*NOTE: One receptor can stimulate many G-proteins*

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11
Q

Once G-protein is activated, the alpha subunit exchanges…

A

GDP (low energy state) for GTP

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12
Q

The exchanged GTP bound alpha-subunit transmits the signal to other cellular components which…

A

Gives an amplified response/keeps amplifying the signal

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13
Q

The activated G-protein will then stimulate…

A

Adenylate cyclase

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14
Q

Activation of adenylate cyclase leads to…

A

Synthesis of cAMP

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15
Q

Binding of epinephrine to the receptor on the cell surface _______ the rate of cAMP production in the cell.

A

Increases

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16
Q

cAMP stimulates phosphorylation of many target proteins, including…

A

Protein Kinase A which controls many responses (GIT, blood, skin, etc.)

17
Q

Protein Kinase A (PKA) has…

A

2 regulatory subunits and 2 catalytic components

18
Q

Binding of cAMP dissociates which subunits of the PKA?

A

R subunits

19
Q

How do you turn this epinephrine signal off? (3 ways)

A
  1. G alpha has ability to reset itself by cleaving the bound GTP to GDP to terminate the G-protein
  2. cAMP phosphodiesterase converts cAMP to AMP which prevents activation of PKA
  3. The epinephrine-beta-adrenergic receptor is reversible. Dissociates/resets
20
Q

What is Cholera?

A

Produces a toxin that modifies one specific G-protein and locks it in the active form. Net result is a loss of NaCl and water into the intestine

*Severe diarrhea that can kill you within 24 hours

21
Q

Pertussis Toxin (Whooping Cough)

A

Modifies a G-protein by trapping it in the inactive form so you cannot turn on a signaling pathway so it is rendered inactive

22
Q

Hydrolysis of Phosphatidylinositol Biphosphate by Phospholipase C generates 2 secondary messengers

A

DAG and IP3

23
Q

Binding of IP3 in the ER causes what? What is an example of this pathway?

A

Release of Ca2+ out of the ER and raise how much calcium is present in the cytoplasm

Ex: Vasopressin binding to a 7TM

24
Q

DAG with calcium activates…

A

Protein kinase C

25
Q

The human growth hormone will bind to a receptor and causes it to…

A

Dimerize which results in the turning on of JAK2 and they phosphorlate each other, which turns on kinases that then phosphorylate other targets.

26
Q

RTK

Describe the pathway of this receptor.

What does it lead to?

A

Forms dimers that lead to cross-phosphorylation and activation of two intracellular kinase domains.

Leads to activation of Ras, which turns on specific targets that activate growth

One molecule - no separate kinase involved

27
Q

Ras is a key component of…

A

The EGF pathway

28
Q

Ras is a member of the family of small ______, which control a variety of cellular processes.

Active when bound to ____ and inactive when bound to ____.

A

G proteins or GTPases

Active: GTP

Inactive: GDP

29
Q

The hormone insulin is secreted when…

A

Blood glucose levels are high

(Regulates metabolism)

30
Q

Insulin receptor is an…

A

RTK

31
Q

The RTK dimers form on insulin binding and phosphorylate to turn on and activate a series of molecules that leads to the activation of the kinase ______.

A

AKT which phosphorylates glucose transporter GLUT4, increasing glucose uptake by the cells and enzymes that convert glucose into glycogen.

32
Q

Insulin signaling is turned off by…

A

Action of phosphotases removing phosphates from activated proteins in the insulin pathway (“Timers”)

33
Q

What is calmodulin?

A

Ca2+ sensor with 4 calcium binding sites called EF hands and activates targets such as pumps.

34
Q

Too much or mutated RTK or Ras can lead to…

A

Cancer

35
Q

What is an oncogene?

A

A mutated proto-oncogene leading to unrestrained growth

36
Q

Proto-oncogenes…

A

Control cell growth

37
Q

What may be an effective anti-cancer drug and why?

A

Kinase inhibitors

CML (Leukemia) can be caused by overexpression of a tyrosine kinase, if inhibited, growth would be stunted.

38
Q

Negative free energy will always be…

A

Spontaneous